Effects of Ninjin'yoeito on Human CYP3A and Mouse CYP3A Activity.

Ninjin'yoeito (NYT) is widely used clinically for the management of patients with frailty and other multiple symptoms. NYT is often administered with other drugs; however, little information is available on its drug interactions. Previous studies using human liver microsomes have reported that constituents of NYT either inhibit (schisandra fruit, cinnamon bark, glycyrrhiza, and poria sclerotium) or induce (schisandra fruit and glycyrrhiza) CYP3A4 expression. Herein, we conducted in vitro and in vivo studies targeting human CYP3A and mouse CYP3A to elucidate the effects of NYT coadministration with other drugs on hepatic drug metabolism. In an inhibition study using human liver microsomes, NYT showed concentration-dependent reversible inhibition and time-dependent inhibition. Furthermore, in an induction study using frozen human hepatocytes, the addition of 0.01-0.1 mg/mL NYT resulted in a concentration-dependent increase in CYP3A gene expression. Contrarily, no significant changes in CYP3A substrate blood concentrations were observed between untreated mice and mice that received either a single dose of NYT or repeated doses for 15 days. These results demonstrate that NYT has inhibitory and inductive effects on hepatic CYP3A in vitro, but orally administered NYT does not affect drug metabolism mediated by hepatic CYP3A in vivo in the mouse model. Although there is a little information about drug interactions of NYT, this study provides new evidence for that.

A method for estimating 3-D nuclear parameters using an image taken from a hepatic histopathological section.

A method is described for estimating the 3-D nuclear parameters (3-D nuclear density and average and variance of nuclear radii) from one microscopic image taken from one hepatic histopathological section. The method estimates the probability densities of the parameters, so, not only the expected values but also the confidence intervals, which are important in actual diagnosis, are calculated. Since only one image, which is taken from one histopathological section used in daily diagnosis, is needed, it is convenient for pathologists to use this method. A graphical user interface makes the method easy to use.